Systemic Corticosteroid Effect and Potency

Corticosteroids are a group of hormones that can be classified by 2 primary mechanisms of action at distinct receptors [1].

1. Mineralocorticoid activity results in sodium retention in the renal distal tubule as well as potassium excretion. This results in increased overall sodium balance and increased extracellular fluid volume. Additionally this effect is responsible for increased reactivity to vasoactive compounds and subsequent increases in blood pressure.
2. Glucocorticoid activity results in gluconeogenesis, lipolysis, and hyperglycemia. The glucocorticoid potency of a steroid is directly proportional to its anti-inflammatory potency. Anti-inflammatory effects from corticosteroids are related to reductions in pro-inflammatory cytokine levels as well as reductions in circulating lymphocytes, eosinophils, monocytes, and basophils.

Clinical Implications [1-7]

Table: Relative potency and pharmacokinetics of common systemic corticosteroids (Note: A lower glucocorticoid potency correlates with needing higher mg dosing for anti-inflammatory effects)

• The anti-inflammatory effect of corticosteroids stems from the regulation of gene expression and subsequent changes in protein production. Because of this delayed clinical effect, for most indications intravenous (IV) and oral administration have a similar onset of action and efficacy.
• For most asthma and COPD exacerbations requiring systemic steroids, the equivalent of prednisone 40-60 mg is recommended. If administered IV, the equivalent dose of methylprednisolone is 40 mg [4].
• Dexamethasone has a significantly longer half-life than other commonly used systemic corticosteroids. A single or 2-day course of dexamethasone (10-12 mg for adults; 0.06 mg/kg for children) may be appropriate for asthma exacerbations when adherence to a 5-day regimen of prednisone is a concern [5-7].

References

1. Schimmer BP, Funder W. Adrenocorticotropic Hormone, Adrenal Steroids, and the Adrenal Cortex. In: Brunton LL, Hilal-Dandan R, Knollmann BC. eds. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e New York, NY: McGraw-Hill Medical; 2018.
2. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of Chronic Obstructive Pulmonary Disease: 2019 Report.
3. National Asthma Education and Prevention Program: Expert Panel Report III: Guidelines for the diagnosis and management of asthma. Bethesda, MD. National Heart, Lung, and Blood Institute, 2007. (NIH publication no. 08-4051)
4. Lindenauer PK, Pekow PS, Lahti MC et al. Association of corticosteroid dose and route of administration with risk of treatment failure in acute exacerbation of chronic obstructive pulmonary disease. JAMA. 2010;303(23):2359. PMID: 20551406
5. Kravitz J, Dominici P, Ufberg J et al. Two days of dexamethasone versus 5 days of prednisone in the treatment of acute asthma: a randomized controlled trial. Ann Emerg Med. 2011 Aug;58(2):200-4. PMID: 21334098
6. Paniagua N, Lopez R, Muñoz N et al. Randomized Trial of Dexamethasone Versus Prednisone for Children with Acute Asthma Exacerbations. J Pediatr. 2017 Dec;191:190-196.e1. PMID: 29173304
7. Rehrer MW, Liu B, Rodriguez M et al. A randomized controlled noninferiority trial of single dose of oral dexamethasone versus 5 days of oral prednisone in acute adult asthma. Ann Emerg Med. 2016;68(5):608–613. PMID: 27117874